ArticleThe Journal of clinical investigation2014
Combined SFK/MEK inhibition prevents metastatic outgrowth of dormant tumor cells.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers.
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Who cites it
101 citing papers in PubMed, 141 citations in OpenAlex.
- Mechanisms of breast cancer dormancy in bone metastasis.Clinical & experimental metastasis · 2026Review
- Regulating the dormancy of cancer stem cells: a novel approach to preventing cancer relapse.Cell death & disease · 2026Review
- Clinical Significance of Copper Chaperone for Superoxide Dismutase in Colorectal Cancer.Annals of gastroenterological surgery · 2026Article
- Immune Niche Formation Reveals Mechanisms of Tumor Dormancy and Targeting Opportunities.Research square · 2026Article
- Upregulation of Sox2 Following Saracatinib Treatment Contributes to a Resistant Phenotype in Colorectal Cancer Cells under Growth Factor-Supplemented Conditions.Oncology research · 2026Article
- Collagen dynamics in the breast cancer tumor microenvironment and therapeutic perspectives.Discover oncology · 2025Review
- Cancer Cell Dormancy in the Bone Microenvironment.Current osteoporosis reports · 2025Review
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- Understanding Tumor Dormancy: from Experimental Models to Mechanisms and Therapeutic Strategies.Biomolecules & therapeutics · 2025Review
- Clinical applications of circulating tumor cells in metastasis and therapy.Journal of hematology & oncology · 2025Review
- Enter sandman: how to tackle dormant breast cancer cells.Medical oncology (Northwood, London, England) · 2025Review
- Immune Niche Formation in Engineered Mouse Models Reveals Mechanisms of Tumor Dormancy.bioRxiv : the preprint server for biology · 2025Article
- Microenvironmental Regulation of Dormancy in Breast Cancer Metastasis: "An Ally that Changes Allegiances".Advances in experimental medicine and biology · 2025Review
- Sleepyhead, deadly awakening: the dynamics of metastatic organotropism, tumor dormancy and therapeutic implications.Frontiers in oncology · 2025Review
- Review
- Review
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- How much do we know about the metastatic process?Clinical & experimental metastasis · 2024Review
- Outlook and opportunities for engineered environments of breast cancer dormancy.Science advances · 2024Review
41 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Breast cancer (BC) can recur as metastatic disease many years after primary tumor removal, suggesting that disseminated tumor cells survive for extended periods in a dormant state that is refractory to conventional therapies. We have previously shown that altering the tumor microenvironment through fibrosis with collagen and fibronectin deposition can trigger tumor cells to switch from a dormant to a proliferative state. Here, we used an in vivo preclinical model and a 3D in vitro model of dormancy to evaluate the role of Src family kinase (SFK) in regulating this dormant-to-proliferative switch. We found that pharmacological inhibition of SFK signaling or Src knockdown results in the nuclear localization of cyclin-dependent kinase inhibitor p27 and prevents the proliferative outbreak of dormant BC cells and metastatic lesion formation; however, SFK inhibition did not kill dormant cells. Dormant cell proliferation also required ERK1/2 activation. Combination treatment of cells undergoing the dormant-to-proliferative switch with the Src inhibitor (AZD0530) and MEK1/2 inhibitor (AZD6244) induced apoptosis in a large fraction of the dormant cells and delayed metastatic outgrowth, neither of which was observed with either inhibitor alone. Thus, targeting Src prevents the proliferative response of dormant cells to external stimuli, but requires MEK1/2 inhibition to suppress their survival. These data indicate that treatments targeting Src in combination with MEK1/2 may prevent BC recurrence.
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Registered trials
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